PubMed: Pseudocannabinoid H4CBD improves glucose response during advanced metabolic syndrome in OLETF rats independent of increase in insulin signaling proteins

PubMed: Pseudocannabinoid H4CBD improves glucose response during advanced metabolic syndrome in OLETF rats independent of increase in insulin signaling proteins

Am J Physiol Regul Integr Comp Physiol. 2023 Oct 30. doi: 10.1152/ajpregu.00125.2022. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) use has grown exponentially more popular in the last two decades, particularly amongst older adults (>55 years), though very little is known about the effects of CBD use during age-associated metabolic dysfunction. Additionally, synthetic analogues of CBD have generated great interest because they can offer a chemically pure product, which is free of plant-associated contaminants. To assess the effects of a synthetic analogue of CBD (H4CBD) on advanced metabolic dysfunction, a cohort of 41-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were administered 200 mg H4CBD/kg by oral gavage for 4 weeks. Animals were fed ad libitum and monitored alongside vehicle-treated OLETF and Long-Evans Tokushima Otsuka (LETO) rats, the lean-strain controls. An oral glucose tolerance test (oGTT) was performed after 4 weeks of treatment. When compared to vehicle-treated OLETF rats, H4CBD decreased body mass (BM) by 15%, which was attributed to a significant loss in abdominal fat. H4CBD reduced glucose response (AUCglucose) by 29% (p<0.001) and insulin resistance index (IRI) by 25% (p<0.05) compared to OLETF rats. However, H4CBD did not statically reduce fasting blood glucose or plasma insulin, despite compensatory increases in skeletal muscle native insulin receptor (IR) protein expression (54%; p<0.05). H4CBD reduced circulating adiponectin (40%; p<0.05) and leptin (47%; p<0.05) and increased ghrelin (75%; p<0.01) compared to OLETF. Taken together, a chronic, high dose of H4CBD may improve glucose response, independent of static changes in insulin signaling and these effects are likely a benefit of the profound loss of visceral adiposity.

PMID:37899754 | DOI:10.1152/ajpregu.00125.2022

https://pubmed.ncbi.nlm.nih.gov/37899754/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20231030072135&v=2.17.9.post6+86293ac October 30, 2023 10:00 am